Link between autoimmune therapy, preterm birth is largely due to confounding

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.